Laboratory studies using direct calorimetry, a technique which is no longer either rare or difficult, have shown no essential differences between men and women who gain weight easily and the always lean. Both groups gained weight similarly when overeating by 1,000 kcal·d-1. Thermogenic responses to eating and the energy losses in food and urine were similar in the overweight and lean. Daily sedentary energy expenditure is a function of fat-free mass, and fat-free mass increases with obesity. During exercise, calorimetry has shown that heat losses are not always exactly matched to heat production as calculated from respiratory gas exchange, but a 24-h exercise period with a cycle ergometer showed reasonable energy balance when subjects ate as much as they spent. During weight loss from restricting food intake by 1,000 kcal·d-1, calorimetry showed a 12% reduction in sedentary energy expenditure. Based on calorimetry studies and other evidence in the literature, exercise increases energy expenditure, it may eliminate the reduced energy expenditure of caloric restriction, and it can increase muscle mass and thus increase both fat-free mass and daily expenditure.